Ventral pallidum GABA and glutamate neurons drive approach and avoidance through distinct modulation of VTA cell types

• Published in: Nature communications Vol. 15; no. 1; pp. 4233 - 18
• Main Authors: Faget, Lauren, Oriol, Lucie, Lee, Wen-Chun, Zell, Vivien, Sargent, Cody, Flores, Andrew, Hollon, Nick G., Ramanathan, Dhakshin, Hnasko, Thomas S.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18.05.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/378/1662; 631/378/1788; 631/378/3920; 64/60; 82/1; 82/51; 96/10; 96/35; 96/44; 96/63; Animals; Aversion; Avoidance; Avoidance behavior; Avoidance Learning - physiology; Basal Forebrain - metabolism; Basal Forebrain - physiology; Behavior, Animal - physiology; Dopamine; Dopamine - metabolism; Dopaminergic Neurons - metabolism; Dopaminergic Neurons - physiology; GABAergic Neurons - metabolism; GABAergic Neurons - physiology; gamma-Aminobutyric Acid - metabolism; Globus pallidus; Glutamic Acid - metabolism; Humanities and Social Sciences; Hypothalamus (ventromedial); Male; Mice; Mice, Inbred C57BL; multidisciplinary; Neurons; Neurons - metabolism; Neurons - physiology; Nucleus accumbens; Nucleus Accumbens - cytology; Nucleus Accumbens - metabolism; Nucleus Accumbens - physiology; Pallidum (ventral); Reinforcement; Reward; Science; Science (multidisciplinary); Stimulation; Ventral Tegmental Area - cytology; Ventral Tegmental Area - metabolism; Ventral Tegmental Area - physiology; Ventral tegmentum; γ-Aminobutyric acid
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-48340-y

The ventral pallidum (VP) contains GABA and glutamate neurons projecting to ventral tegmental area (VTA) whose stimulation drives approach and avoidance, respectively. Yet little is known about the mechanisms by which VP cell types shape VTA activity and drive behavior. Here, we found that both VP GABA and glutamate neurons were activated during approach to reward or by delivery of an aversive stimulus. Stimulation of VP GABA neurons inhibited VTA GABA, but activated dopamine and glutamate neurons. Remarkably, stimulation-evoked activation was behavior-contingent such that VTA recruitment was inhibited when evoked by the subject’s own action. Conversely, VP glutamate neurons activated VTA GABA, as well as dopamine and glutamate neurons, despite driving aversion. However, VP glutamate neurons evoked dopamine in aversion-associated ventromedial nucleus accumbens (NAc), but reduced dopamine release in reward-associated dorsomedial NAc. These findings show how heterogeneous VP projections to VTA can be engaged to shape approach and avoidance behaviors. Ventral pallidum GABA and glutamate neuron activation drives approach and avoidance, respectively. Here, the authors show that both ventral pallidum cell types are activated during approach to reward and by aversive stimuli, but elicit opponent effects on VTA cell-type activity.